AB1675 DEEP PHENOTYPING OF IMMUNE MICROENVIRONMENT IN ULCERATIVE COLITIS BY INTEGRATIVE SYSTEMS ANALYSIS
Authors: Q. Wang, M. R. Chen, J. W. Hao, M. J. Chang, S. X. Zhang, Q. Yu, P. F. He
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ulcerative colitis (UC) is an inflammatory bowel disease characterized by idiopathic and recurrent mucosal inflammation [1]. The pathogenesis is multifactorial, involving genetic susceptibility, epithelial barrier defects, dysregulation of the immune response, and environmental factors. UC is a highly heterogeneous disease [2]. Despite efforts to characterize disease subgroups and predict differential outcomes in UC patients, disease heterogeneity is not adequately translated into current clinical subclassifications. <h3>Objectives</h3> This study seeks to unravel this complexity by using an integrated systems approach that classifies UC patients into different phenotypes based on the immune microenvironment, capable of providing new insights into the development of stratified therapies. <h3>Methods</h3> RNA sequencing datasets of 602 colon tissue samples from 455 patients with UC and 147 healthy controls (HC) was imported from GEO database. The microarray datasets were transformed into immune cell components by CIBERSORT, and patients were stratified by a consensus clustering algorithm. Then, the cellular characteristics of the subtypes and the overall role of specific pathways were determined by immune cell infiltration and pathway enrichment. The clinical characteristics of the different subtypes were also analyzed to clarify the characteristics of these classifications. <h3>Results</h3> Patients can be classified into two distinct immune phenotypes (Subtype A, B) based on their specific RIME, which have different cellular and pathway characteristics. (Figure A, B) The results show that Subtype A is mainly enriched in immune cells such as B cells, CD8+ T cells, CD4+ memory T cells, DC cells, macrophages, mast cells and plasma cells. Acidic granulocytes and neutrophils were more active in Subtype B. It was also significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway in Subtype B. In contrast, Subtype A showed a strong enrichment for most inflammatory pathways B cell and T cell receptor signaling, IL-17 signaling pathway, TNF, and interleukin 4 and interleukin 13 signaling pathway. (Figure 1 D, E) In addition, there was a significant difference between molecular subclassification and disease status, with Subtype A being more active in patients (69.3% of Subtype A vs.30.6% of Subtype B subtypes in 137 cases), while inactive patients, Subtype B were more prevalent (44.8% of Subtype A vs. 55.2% of Subtype B in 105 cases). (Figure 1C) <h3>Conclusion</h3> Analysis of the immune microenvironment of colonic mucosal tissue provides good insight into the pathophysiological characteristics of UC. These results can be used as a model for future studies. the response and clinical outcomes of patients with different classification need to be further investigated. <h3>References</h3> [1]Ghosh S, Shand A, Ferguson A. Ulcerative colitis. BMJ (Clinical research ed). 2000;320(7242):1119-23. [2]Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet (London, England). 2012;380(9853):1606-19. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.